Alzheimer´s disease (AD) is a neurodegenerative disorder characterized by
progressive memory loss, cognitive impairment, and at the molecular level, by the
presence of neurofibrillary tangles (NFTs). As opposed to degeneration, it is known
that some specific regions of the brain contain neural stem cells (NSCs) able to
produce neurons during adulthood. Wnt/β-catenin signaling has been described as a
key pathway modulating the balance between NSC proliferation and differentiation.
Wnt signaling is regulated by glycogen synthase kinase 3 (GSK3) that is constitutively
active in the cells, keeps β -catenin phosphorylated on serine and threonine residues,
and controls its proteosomal-mediated degradation. This raises the question whether
inhibition of GSK3β activity, β -catenin stabilization, and therefore, pharmacological
activation of endogenous neurogenesis would be a plausible therapeutic strategy for
treating AD patients. In this chapter, we herein review the Wnt/β-catenin signaling
and evaluate the strategy of inhibiting GSK3β in the disease.
Keywords: Neurofibrillary tangles, β -amyloid, drug therapy, GSK3 inhibitor,
lithium, neural stem cells, diabetes, AGEs, RAGE, cognitive impairment.
